HTX-011 Administration Study in Planned Caesarean Section Procedure

A Phase 2 Open-Label Study of the Pharmacokinetics (PK) and Safety of HTX-011 Administered Postpartum to Women Undergoing a Planned Caesarean Section

This is a Phase 2, open-label study to evaluate the PK and safety of HTX-011 in women undergoing a planned C-section.

Study Overview

• Status: Completed
• Conditions: Analgesia
• Intervention / Treatment: Drug: Ibuprofen; Device: Luer Lock Applicator; Drug: HTX-011; Drug: HTX-011; Drug: Acetaminophen

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Sheffield, Alabama, United States, 35660
      • Helen Keller Hospital
  • California
    • San Diego, California, United States, 92123
      • Sharp Mary Birch Hospital for Women and Newborns
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • UPMC Magee-Womens Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Is expected, at the time of Screening visit, to deliver a single neonate.
• Is scheduled to undergo a planned C-section surgery with a low transverse skin incision (eg, Pfannenstiel).
• Has American Society of Anesthesiologists (ASA) Physical Status of I, II, or III.
• Agrees to practice abstinence or use double-barrier contraception in the event of sexual activity and commits to the use of an acceptable form of birth control for 30 days after HTX-011 administration.
• Agrees to refrain from the use of breast milk from this pregnancy in any manner.

Exclusion Criteria:

• Has planned to breastfeed her neonate at any time during the 28-day period after HTX-011 administration.
• Has had a prior full-term pregnancy with unsuccessful breast milk expression.
• Has a planned concurrent surgical procedure.
• Has a contraindication or a known or suspected history of hypersensitivity or clinically significant idiosyncratic reaction to required study medications.
• Has been administered bupivacaine within 5 days prior to the scheduled surgery.
• Has been administered any local anesthetic within 72 hours prior to the scheduled surgery.
• Has been administered systemic steroids within 5 half-lives or 10 days prior to administration of study drug.
• Has initiated treatment with study medications within 1 month prior to study drug administration that can impact pain control.
• Has taken any NSAIDs within least 10 days prior to the scheduled surgery.
• Has current significant placental abnormality/complications including, but not limited to, placenta previa or placenta accreta.
• Has a medical condition such that, in the opinion of the Investigator, participating in the study would pose a health risk to the subject or confound the postoperative assessments.
• Has uncontrolled anxiety, psychiatric, or neurological disorder.
• Had a malignancy in the last year, with the exception of nonmetastatic basal cell or squamous cell carcinoma of the skin or localized carcinoma in situ of the cervix.
• Has a known or suspected history of drug abuse, a positive drug screen on the day of surgery, or a recent history of alcohol abuse.
• Previously participated in an HTX-011 study.
• Received an investigational product or device in a clinical trial within 30 days or within 5 elimination half-lives.
• Weight is <50 kg at the time of Screening visit.
• In the Investigator's judgment, subject is likely to have been morbidly obese prior to her pregnancy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment Group 1; A single dose of HTX-011 administered via instillation into the surgical site.	Device: Luer Lock Applicator; Applicator for instillation.; Drug: HTX-011; 300 mg; Other Names: Cohort 1; Drug: HTX-011; 400 mg; Other Names: Cohort 2
Experimental: Treatment Group 2; A single dose of HTX-011 administered via instillation into the surgical site and a scheduled non-opioid multimodal analgesic (MMA) regimen.	Drug: Ibuprofen; 400 mg; Device: Luer Lock Applicator; Applicator for instillation.; Drug: HTX-011; 300 mg; Other Names: Cohort 1; Drug: HTX-011; 400 mg; Other Names: Cohort 2; Drug: Acetaminophen; 975 mg to 1 g

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Maximum plasma concentration (Cmax) of bupivacaine, meloxicam, dimethyl sulfoxide (DMSO) and HTX-011 polymer	Day 1 to Day 16 for Cohort 1; Day 1 to Day 11 for Cohort 2
Time of maximum plasma concentration (Tmax) of bupivacaine, meloxicam, DMSO and HTX-011 polymer	Day 1 to Day 16 for Cohort 1; Day 1 to Day 11 for Cohort 2
Half life (t1/2) in plasma of bupivacaine, meloxicam, DMSO and HTX-011 polymer	Day 1 to Day 16 for Cohort 1; Day 1 to Day 11 for Cohort 2
Half life (t1/2) in milk of bupivacaine, meloxicam, DMSO and HTX-011 polymer	Day 1 to Day 16 for Cohort 1; Day 1 to Day 11 for Cohort 2
Amount of analyte excreted in breast milk over time (Ae)	Day 1 to Day 16 for Cohort 1; Day 1 to Day 11 for Cohort 2
Fraction of dose excreted in breast milk over time (Fe)	Day 1 to Day 16 for Cohort 1; Day 1 to Day 11 for Cohort 2

Secondary Outcome Measures

Outcome Measure	Time Frame
Mean area under the curve of the NRS pain scores through 72 hours (AUC0-72).	72 hours
Incidence of treatment-emergent adverse events (TEAEs).	28 Days.

Collaborators and Investigators

• Sponsor: Heron Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): June 24, 2019
• Primary Completion (Actual): December 3, 2021
• Study Completion (Actual): December 27, 2021

Study Registration Dates

• First Submitted: May 9, 2019
• First Submitted That Met QC Criteria: May 16, 2019
• First Posted (Actual): May 20, 2019

Study Record Updates

• Last Update Posted (Actual): March 14, 2022
• Last Update Submitted That Met QC Criteria: March 11, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: caesarean section; postoperative pain; C-section
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Antipyretics; Acetaminophen; Ibuprofen
• Other Study ID Numbers: HTX-011-220

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes